How to perform a BD exam and improve donor management Panayiotis N. Varelas, MD, PhD Director Neuro-ICU Senior Staff Neurology / Neurosurgery Henry Ford

How to perform a BD exam and improve donor management

Panayiotis N. Varelas, MD, PhD

Director Neuro-ICU

Senior Staff Neurology / Neurosurgery

Henry Ford Hospital

Associate Professor of Neurology

Wayne State University

Detroit, MI

Topics for discussion

• Management before BD is declared

• How BD exam is performed

• How to approach the family

• Management after BD is declared

I have received speaker honoraria and holds stock options from The Medicines Company. The same company has sponsored research for which he served as primary investigator. He also receives royalties from the publication of the book Seizures in the ICU, is an editorial board member of Neurocritical Care and is serving in the advisory board of Gift of Life of Michigan.

Potential conflicts:I have received speaker honoraria and hold stock options from The Medicines Company, which has sponsored my research. I also receive royalties from the publication of the book Seizures in the ICU, I am an editorial board member of Neurocritical Care and serving in the advisory board of Gift of Life of Michigan.

HFH Management RecommendationsBEFORE BD Declaration

HFH Management RecommendationsBEFORE BD Declaration

• These recommendations are to be discussed, agreed upon and ordered by the ICU Primary Team (Senior Staff) and collaboratively implemented by the ICU Primary team, Gift of Life representative, and ICU nursing.

• These recommendations are not orders and should not be used as such. If a decision is made to utilize one or more of these recommendations, an order must be written by the physician.

• Methods for attaining goals are just recommendations – they should not be used if they are contraindicated to the patient’s condition or contrary to patient’s /family’s advance directives

HFH Management RecommendationsBEFORE Brain Death Declaration

• MAP maintained ≥ 60 mmHg – Prevent Hypotension• Keep CPP > 70, if an ICP monitor is in place

– Maintenance IV Fluid: 0.9% NS with 20 mEq KCl @ 100-150ml/hr. (Saline may need to be adjusted for Na+ greater than 160, see below.)

– For hypovolemia: Bolus with 500mL 0.9% NS until MAP sustains ≥60 mmHg.

– Start Dopamine and titrate to maintain MAP ≥ 60 mmHg (max 20 mcg/kg/min). Always notify the physician when starting pressors or inotropes or transfusing blood products.

– If Dopamine is at 20 mcg/kg/min, CVP greater than 10, and MAP/CPP remains less than 60 mmHg, consider norepinephrine infusion. Titrate to clinical effect (max 20 mcg/min)

– If Hct ≤ 25%, recommend 1 unit of PRBC’s over 1 hour, repeat as necessary to maintain HCT ≥ 25% or hemoglobin > 7.0.


• Hypertension– Use IV Hydralazine prn. Avoid beta-blockers.

• Hypothermia– Warming blanket to maintain core body temp between 36.5° – 37.2° C,

except for pts with induced-hypothermia.

• Diabetes Insipidus (DI)– For urinary output greater than 4 mL/kg/hr X 2 hrs AND Na+ > 155

and rising, recommend Vasopressin drip or replace urine output mL/mL:

If Na+ > 160, use Half NS (0.45%) for replacementIf Na+ ≤ 160, use NS 0.9% for replacementAlways notify the physician if pt hypotensive (CPP <

70, MAP < 60) or tachycardic (HR > 90)


• Hypoxemia– Titrate FiO2 to maintain SaO2 greater than 98% or

PaO2 > 300 on FiO2 1.00

– Tidal Volume at 6 mL/kg

– Add PEEP of 5-8 cmH2o

– Rate adjusted to maintain normal pH (7.35-7.45)

– Suction and turn patient q 1-2 hrs

– Initiate Chest Percussion and Vibration q 1-2 hrs

– Albuterol Nebulizers: 2.5mg q 4 hrs.

How to perform a BD exam?

Current BD criteria in the US

• Responsibility left to individual institutions: Each hospital has to develop its own criteria, based on

• State laws criteria based on “accepted medical standards”, based on

• President’s Commission (1981), Uniform Determination of Death Act (UDDA, 1993), AAN (2010) or other Societies recommendations, which are “advisory” and carrying the weight of “guidelines” rather than standards

HFH: determination of brain death

• Determination of “death by brain criteria” in accordance with MI law

• Two different physicians, licensed in MI: 1) The primary senior staff physician

2) Senior staff from Neurology or NS

or designated physician under direct supervision, i.e resident, fellow

Determination of brain death - Process

• GCS ≤ 5 GOL notified within 1 hour• If All prerequisites are met

• Clinical evaluation:Cerebral unresponsiveness: deep, irreversible comaAbsence of brainstem reflexesAbsence of respiration (Apnea test)

• ± Confirmatory testing

Determination of brain death - Prerequisites

• Established & sufficient cause of irreversible coma• Age 7 days• Exclusion of any complicating condition confounding

clinical assessment:

Absence of deep sedation or peripheral nerve or muscle dysfunction, i.e., (+) TOF, if NM blockade

ToxScreen: ETOH < 80mg%, < 10g/ml, drugs? Temp-core 32.2oC (90oF) SBP 90 mmHg or MAP > 60 mm Hg or age-specific

normotensive range in children Severe electrolyte, acid-base or endocrine disturbances

Suspicion of drugs – toxins?• Administer antidotes

• Narcotics naloxone• Benzodiazepines flumazenil• Carbon monoxide oxygen• Carbon disulfide, cyanide, hydrogen sulfide amyl nitrite

• Declare brain death if traces of drug are found below therapeutic level

• Unable to quantify drug/poison observe for x 5 half lives

• Unknown, but high suspicion 48 hrs observation, if no confirmatory study

Wijdicks Brain Death 2001

Pitfall: Effect of hypothermia on sedative metabolism

Figure A shows the time course changes in concentration of Midazolam in brain-injured patients undergoing hypothermic therapy As shown in (A) concentration of the agent increased linearly until Body Temp reached 35 °C, after which the levels decrease profoundly when Body Temp rose to 36 °C, even during continuous administration of Midazolam.

(B) Depicts the time course changes in concentration of Midazolam in brain-injured patients with normothermic therapy. In the figure, the concentration of the agent increased at 24 h after administration, then plateaued from 72 h, lasting until 216 h, during continuous infusion.

Fukuoka et al, Resuscitation 2004

Clinical Examination - Coma

• Lack of responsiveness to supraorbital nerve, nail-bed or TMJ pressure

• Pitfalls:Uncoordinated, non-integrated into posturing

responses = i.e. 2o to spinal cord reflexesPartial eye opening in response to ipsilateral

nipple twisting 5 sec later (sympathetic fibers to Muller’s muscle?) (Santamaria et al., 1999)

Clinical Examination - Reflexes

• Mid-position (4-6 mm) or dilated pupils• Pitfalls: Drugs that influence pupils: Topical application of mydriatics Atropine in IV doses 0.03 mg/kg slight mydriasis,

but (+) reaction to light (Goetting et al., 1991)

Escalating doses of non-depolarizing paralytics lead from reversible to non-reversible mydriasis

(Schmidt et al., 2000)


• Oculocephalic reflex (Cervico-occular, COR)

• Cold calorics (VOR)

• Pitfalls: or absent if: Toxic levels of aminoglycosides,

tricyclics, anticholinergics, antiepileptics Orbital edema Battle’s sign (ipsilaterally)


• Corneal, blinking to threat• Grimacing to pain, jaw reflex Pitfall: facial myokymia/fibrillation from

muscle denervation may mimic facial movements• Nasal tickle (V2 - XI)• Gag, cough• Over-breathing• Atropine test: tachycardia (↑ HR > 3%) to 2-3mg

IV atropine (Huttemann et al., ICM 2000)

Apnea test

• Always with the second BD exam

• Pre-oxygenation 100% FiO2

• PaCO2 target: 60 mmHg or [baseline + 20]

• PaCO2 by 3-6 mm Hg/min

• Hypothermia ( CO2 production, left shift O2 dissociation curve) normothermia

• Hypotension SBP goal 90 mm Hg

Pre-admission or “normal” level for the pt

Apnea test - Solutions• Unable to complete the test??

repeat after correcting the problem clinical exam + confirmatory test use tricks:

CO2 augmentation (1 L/min) – PaCO2 > 60 mmHg within 2 min (Lang, 1995)

Bulk diffusion (set rate = 0, CPAP = 0, 100% FiO2, 40-60 L/min continuous flow) - 22/24 pts completed the test

(al Jumah et al., 1992)

T-piece (12 L/min) with CPAP valve (10 cm H2O) – less desaturation with T-piece compared to cannula inside ETT or T-piece alone (Levesque et al., CCM 2006)

ADVICE: perform apnea test even if pt on high FiO2 and draw ABGs as O2 Sat reaches 90%!

HFH: determination of brain death - Observation period between 2 clinical exams

• Structural brain lesions: 2 Clinical exams 6 hours + apnea optional ConfTest

• Catastrophic structural brain lesion: 1 exam + ConfTest (CBF test) + apnea

• Ischemic/anoxic injury: 2 Clinical exams 24 hours + apnea optional ConfTest (for ex. if neuroimaging inconclusive)

HFH: determination of brain death - Observation period between 2 clinical exams

(continue)• Children 1 year – 18 years: 2 Clinical exams 12

hours + apnea ( optional ConfTest)• Children 2 months – 1 year: 2 Clinical exams

24 hours + apnea + ConfTest• Neonates 7 days – 2 months: 2 Clinical exams

48 hours + apnea + ConfTest (2 EEGs 48 hours apart or CBF study, if equivocal)

• Pregnant women: no BD exam or test, until confirmation of viability of fetus

Confirmatory tests may be required

• Confirmatory Tests “are recommended”:

1. Normal or inconclusive CTOH/MRI

2. COPD or sleep apnea- ? chronic PaCO2

3. Inconclusive or indeterminable apnea test

4. Children

5. Inability to perform full clinical exam

6. Severe facial trauma (ex. Racoon eyes)

Relevant racoon eyes

And NOT…

Confirmatory tests may be required (continue)

7. Preexistent abnormal/surgical pupil8. Severe cranial neuropathies9. Toxic/therapeutic level of CNS

depressants, neuromuscular blocking agents, aminoglycosides, anticholinergics

10. (?) complex/integrated motor activity11. Injury as a result of crime (not at HF!)12. If only one brain death exam is required (as @ Henry Ford!!)

Electroretinogram

SPECT with 99mTc-HMPAO99mTc scintigraphy

Clinical Questions

1. Are there patients who fulfill the clinical criteria of brain death who recover brain function?

2. What is an adequate observation period to ensure that cessation of neurologic function is permanent?

3. Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death?

4. What is the comparative safety of techniques for determining apnea?

5. Are there new ancillary tests that accurately identify patients with brain death?

BRAIN DEATH

Approaching the family

AND NOT DISCUSSING ABOUT DONATION!!!

Consent rates

• Average national consent rate 45-50%

• Early referral when BD is imminent

• Suitability for donation relies on OPO

(Franz et al., 1997, DeJong et al., 1998)

Consent rates

• Factors improving donation rates:1. Discussion in a quite environment2. Trained requester (i.e., OPO)3. Decoupling = family understands & accepts BD

before any donation mentioned (Gortmaker

et al., 1998)

4. Within 30 min after BD notification (because if simultaneous donation rate by 20-40% !)

(Niles & Mattice, 1996)

NICU Brain Death and Organ Donation Request Policy

(Helms et al. Neurology 2004) • Donation was not discussed prior to brain death• Brain death declared according to hospital and

AAN policies• Family informed and brain death process

explained by treating attending physician• Physician does not bring up donation to family

and leaves the room• Procurement coordinator (OPO) makes the request

Organ and tissue donation consent rates 21 months before and 21 months after the institution of policy change

(Helms et al. Neurology 2004)

Before %

After % Odds ratio, 95% CI

p value

NICU

Eye 17.1 30.8 1.5, 0.6-3.6 0.5

Bone & Tissue 10.4 37.3 5.1, 1.7-15.9 0.002*

Solid organs 45.6 52.6 1.3, 0.5-3.1 0.7

Total 23.1 36.5 1.9, 1.15-3.15 0.01*

Other units

Eye 16.5 14.2 0.8, 0.5-1.4 0.5

Bone & Tissue 27.1 29.3 1.1, 0.6-2.0 0.8

Solid organs 45.0 61.5 1.9, 0.6-6.4 0.4

Total 19.7 22.4 1.2, 0.9-1.7 0.3


1. Let family know that the 1st BD is done and a 2nd will be performed at X time.

2. No mention about donation !3. If family asks about it, refer them to GOL4. After the 2nd exam (or after the only BD exam),

discuss again with family and explain the results and that the pt is irreversibly and legally dead.

5. Allow time for them to absorb the info, introduce GOL to them and then leave the room


6. If the family decides for donation and consent is signed GOL takes over

Help GOL with tests, procedures

7. If the family decides against donation pt is disconnected from vent within 1 hour

Time from declaration to VF- asystole Time (hours) to asystole

Study

No of

patients <24 24-48 48-72 >72

Jorgensen 1973 63 62% 25% 13%

Mohandas and Chou 1971 25 56% 20% 16% 8%

Hicks and Torda 1979 25 80% 20%

Narimazie 1980 10 60% 40%

Jennett et al 1981 476 36% 31% 11% 23%

Ouaknine 1975 40 “Generally between 1 and 7 days”

Kaste et al 1979 12 “On average 24 hours”

Nishimura 1984 12 “On average six days”

Goulon 1984 23 “Up to 128 hours”

Kenneth Wood, DO, University of Wisconsin, Pallis ABC of Brain Stem Death 1996

Medical management after BD

• Integrative, multi-disciplinary and collaborative approach between OPO and Critical Care Team

• Pre-BD management, aiming at brain function preservation, may compromise other organs and contradict the post-BD/donor management

• Aggressive donor management may allow up to 84% of initially unsuitable donors to yield transplantable organs

(Wheeldon et al., J Heart Lung Transpl 1995)

Kenneth Wood, DO, University of Wisconsin


Hemodynamic Effects of Sympathomimetics

MAP PCWP CO SVR HRDobutamine

Dopamine – moderate

5-10 mcg/kg/min

Dopamine – high

> 10 mcg/kg/min

Isoproterenol

Norepinephrine

Epinephrine

CO – cardiac output; HR – heart rate; MAP – mean arterial pressure; PCWP – pulmonary capillary wedge pressure; SVR – systemic vascular resistance.

Organ Donor - Heart

Myocardial Dysfunction

Sympathetic Surge

• Myocardial necrosis secondary to catecholamines

Hormone Depletion

Subendo Ischemia

• Low circulating levels thyroid and cortisol impair function

• Decreased coronary perfusion pressure precipitates ischemia impairing myocardial function


Changes in Ejection Fraction with Serial Echocardiograms (16)

Zaroff J Heart Lung Txp 2003; 22:383-388

100

90

70

80

60

50

40

30

10

20Eje

ctio

n F

ract

ion

10 250

155 200 30

Time (hours)

Donor Management Assessment

Palac Prog Transplant 2003; 13:42-46

Brain dead patient (< 65 years old)

Assess ventricular function by echocardiogram

Normal

Ejection function 45%

Pulmonary artery catheter placement

Persistently abnormal*

Patient age

Cardiac catheterization

< 40 years

Consider dobutamine echocardiography (viability study)

Reversible dysfunction

No reversible dysfunction

Proceed to transplantNot a donor

> 40 years

Normal Abnormal**

Normal

Repeat echocardiography within 12 hours


Hormonal Therapy (BD Animal Models)

MYOCARDIAL Aerobic Anaerobic Anaerobic Aerobic Function ATP Creatine Phosphate Glycogen Lactate

SYSTEMIC UTILIZATION Glucose Pyruvate Palmitate Lactate Free fatty acids

Pre- Treatment Post Treatment

Insulin

Cortisol

T3

Novitzky Cryobiology 1987; 24: 1-10Novitzky Transplantation 1988; 45:32-36

Rescue Hormone Therapy

• 1 ampule 50% dextrose – 20 u insulin

• 2 grams methylprednisolone

• 20 g levothyroxine infusion 10 g/h

Vasopressor ug/kg/min 11.1 6.4

Heart rate beats/min 120 113

Oxygen consumption ml/min/m2 107 123

Oxygen extraction % 16 18

If 10g/kg/min Vasoactive Support

POSTPRE

Salim Arch Surg 2001; 136:1377-80

Rosendale Transplantation 2003;75:482-487

Aggressive Pharmacologic – Hormonal Replacement

Ware & Matthay, NEJM 2005

Pulmonary Edema

Role of Brain Death in Donor Lung Injury

• “Blast Injury Theory” → Hemodynamic mechanism

• Sympathetic surge

• Transient massive ↑ of hydrostatic pressure with structural damage to pulmonary capillary endothelium

• Sympathetic alteration of capillary permeability

• Cytokines → TNF, IL-1 activate endothelial cells to express ICAM-1 and neutrophil migration to interstitium/alveolar spaces → release ROS and proteolytic enzymes

• ALI/ARDS in 15-20% of severely brain-injured pts

Neurogenic Pulmonary Edema

Inflammatory Response

Left

Right ↑ Pvc ↑ VR ↑PAP ↑Pul Volume

↑ SVR ↓CO ↑LAP

Alvonitis Trasnaplantation 2003; 75:1928-1933

Infection – atelectasis - hemo/pneumothorax

Neurogenic Pulmonary Edema in 11 chacma baboons ICP Autonomic Storm

Catecholamine Excess

Intense Vasoconstriction

• Redistribution blood to RA/RV • SVR 537%

• Adjustment to VR by COR • MAP 196%

• PA flow 25% • Aortic flow 42% LV failure

• mPAP (14 34mmHg) • LAP (8-52mmHg)

• Capillary blood flow arrest

• Blood pooling -72% of total circ. volume in lungs

• Blast injury-disruption of anatomic integrity of pulm capillaries

Right Circuit Left Circuit

Exceeds for 1 minute

Novitzky Ann Thorac Surg 1987; 43:288-294Kenneth Wood, DO, University of Wisconsin


Management of Respiratory Function in the Organ Donor

Goals of mechanical ventilation

FiO2: 0.40

PaO2 > 100 mmHg; or PaO2 > 300 on 100% FiO2

PaCO2: 30-35 mmHg

Arterial pH, 7.35-7.45

Tidal volume: 10-12 ml/kg of predicted body weight

PEEP: 5 cm of water

Peak airway pressure: < 30 - 35 mm Hg

CVP 6-8 mm Hg or PAWP 8-12 mm Hg

Recruitment maneuver: prone or CPAP 40 cm H2O x 30 sec, repeated q 20 min x3

Kirschbaum & Hudson, Prog Transpl 2010

Management of Respiratory Function in the Organ Donor

Goals of bronchoscopy

Evaluate anatomy; Assess for foreign body and assist in removal

Define and locate aspirated material or apparent infection; Clearance of secretions

Goals of pulmonary hygiene

Prevent atelectasis with the use of q 2-4 hr ETT & supraglottic suction, percussion, postural drainage and lung-expansion techniques; Bronchodilators; Paralytics

Use of anti-infective & anti-inflammatory therapy

Use of antibiotics based on results of Gram’s staining of aspirated secretions

Methyl-prednisolone 15 mg/kg IV plus 15 mg/kg IV q 6 hrs

Naloxone 8 mg IV to minimize Neurogenic Pulmonary Edema (?)

Kirschbaum & Hudson, Prog Transpl 2010

Hanna, K. et al. Arch Surg 2011;146:325-328.

Partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FIO2) ratios on admission to the intensive care unit

and following 100% oxygen challenge

• Retrospective, all potential donors within a 5-year period

• 20 pts on ACV & 25 pts on APRV

• ACV: RR 10-12 breaths/min, TV 5-10ml/kg, 40%, PEEP 5

• APRV: 6-10 breaths/min, inspir pressure 20-25 cm H2O and 40%

Donated lungs:

7/40 (18%) in ACV vs

42/50 (84%) in APRV (p < 0.001)

Management of Liver donors

Increased recipient death or re-transplantation:

• ABO incompatibility

• High Na+ levels (> 155 mEq/L)

• Long cold ischemia time

• Large platelet transfusions

• Prolonged recipient PTT

Ploeg et al., Transplant 1993; Figueras et al., Transplant 1996; Kutsogiannis et al., Can J Anaesth 2006

Management of Kidney donors

• + Immunomodulatory effects of catecholamines

Low dose dopamine (< 10 g/kg/min) or epinephrine or vasopressin (< 0.04 U/min)

• Colloids can be used (hydroxyethyl starch)

• Avoid SBP < 80-90 mm Hg

• Keep urine output > 1 ml/kg/hr

• Avoid nephrotoxic drugs

Deman at al., Nephrol Dial Transplant 1999; Dictus et al., Clin Transplant 2009

Intensivist-Led Management of Brain-Dead DonorsIs Associated with an Increase in Organ Recovery

for Transplantation

Singbartl et al, Am J Transpl 2011

In the before period, 66 out of210 (33%) potentially available organs vs. 113 out of 258 (44%) potentiallyavailable organs in the after period, p = 0.008

Island of KEA, Greece

Documents

How to perform a BD exam and improve donor management Panayiotis N. Varelas, MD, PhD Director Neuro-ICU Senior Staff Neurology / Neurosurgery Henry Ford